Villanueva Romero, RaúlGutiérrez Cañas, IreneCarrión Caballo, MarGonzález Álvaro, IsidoroRodríguez Frade, José MiguelMellado, MarioMartínez Mora, María Del CarmenGomáriz, Rosa P.Juarranz Moratilla, Yasmina2023-06-172023-06-172019-05-14Villanueva Romero, R., Gutiérrez Cañas, I., Carrión Caballo, M. et al. «Activation of Th Lymphocytes Alters Pattern Expression and Cellular Location of VIP Receptors in Healthy Donors and Early Arthritis Patients». Scientific Reports, vol. 9, n.o 1, mayo de 2019. Crossref, https://doi.org/10.1038/s41598-019-43717-2.10.1038/s41598-019-43717-2https://hdl.handle.net/20.500.14352/13486Vasoactive Intestinal Peptide (VIP) is an important immunomodulator of CD4+ cells in normal and pathological conditions, which exerts its anti-infammatory and immunomodulatory actions through VPAC receptors, VPAC1 and VPAC2. Only a decrease in the expression of VPAC1 mRNA on Th cells upon activation has been reported. Thus, the deepening in the knowledge of the behavior of these receptors may contribute to the design of new therapies based on their activation and/or blockade. In this study, we describe the expression pattern, cellular location and functional role of VIP receptors during the activation of human Th cells in healthy conditions and in early arthritis (EA). The protein expression pattern of VPAC1 did not change with the activation of Th lymphocytes, whereas VPAC2 was up-regulated. In resting cells, VPAC1 was located on the plasma membrane and nucleus, whereas it only appeared in the nucleus in activated cells. VPAC2 was always found in plasma membrane location. VIP receptors signaled through a PKA-dependent pathway in both conditions, and also by a PKAindependent pathway in activated cells. Both receptors exhibit a potent immunomodulatory capacity by controlling the pathogenic profle and the activation markers of Th cells. These results highlight a novel translational view in infammatory/autoimmune diseases.engAtribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/journal article2045-2322https//doi.org/10.1038/s41598-019-43717-2https://www.nature.com/articles/s41598-019-43717-2open access577.112.6616.72-002Th lymphocytesVasoactive Intestinal PeptideArthritisInmunologíaReumatologíaBioquímica (Biología)2412 Inmunología3205.09 Reumatología2302 Bioquímica